The purpose of the present proposal is to strengthen and expand the research programs on metabolic regulation in neoplasia in the Laboratory for Experimental Oncology. The individual research projects include investigations on (1) regulation of gene expression linked with control of cellular proliferation in mammalian cells; (2) control of purine biosynthesis and catabolism; (3) regulation of pentose phosphate metabolism; (4) control of gene expression in liver tumors; (5) control mechanisms of DNA metabolism in normal and neoplastic proliferation; (6) experimental chemotherapy in tissue culture and in solid tumors (7) control of enzyme turnover through regulation of degradation and regulation of ornithine metabolism; (8) regulation of PRPP amidotransferase by drugs and hormones in normal and cancer cells; (9) role of cyclic nucleotides in neoplasia; (10) properties of purified PRPP amidotransferase from normal and neoplastic cells; (11) regulation of uridylate metabolism in normal, differentiating and cancer cells. These investigations are targeted to elucidate the control of gene expression as metabolic regulation is linked to differentiation in normal and neoplastic cells. BIBLIOGRAPHIC REFERENCES: J. C. Williams, H. P. Morris and G. Weber: Increased UDP kinase activity in rat and human hepatomas. Nature 253, 567-569 (1975). G. Weber, N. Prajda and J. C. Williams: Biochemical strategy of the cancer cell: malignant transformation-linked enzymatic imbalance. Advances in Enzyme Regulation 13, 3-25 (1975).